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2015-06-15

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cc-by (c) Manils Pacheco, Joan et al., 2015
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/113801

Multifaceted role of TREX2 in the skin defense against UV-induced skin carcinogenesis

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https://doi.org/10.18632/oncotarget.4296

Abstract

TREX2 is a 3'-DNA exonuclease specifically expressed in keratinocytes. Here, we investigated the relevance and mechanisms of TREX2 in ultraviolet (UV)-induced skin carcinogenesis. TREX2 expression was up-regulated by chronic UV exposure whereas it was de-regulated or lost in human squamous cell carcinomas (SCCs). Moreover, we identified SNPs in the TREX2 gene that were more frequent in patients with head and neck SCCs than in healthy individuals. In mice, TREX2 deficiency led to enhanced susceptibility to UVB-induced skin carcinogenesis which was preceded by aberrant DNA damage removal and degradation as well as reduced inflammation. Specifically, TREX2 loss diminished the up-regulation of IL12 and IFNγ, key cytokines related to DNA repair and antitumor immunity. In UV-treated keratinocytes, TREX2 promoted DNA repair and passage to late apoptotic stages. Notably, TREX2 was recruited to low-density nuclear chromatin and micronuclei, where it interacted with phosphorylated H2AX histone, which is a critical player in both DNA repair and cell death. Altogether, our data provide new insights in the molecular mechanisms of TREX2 activity and establish cell autonomous and non-cell autonomous functions of TREX2 in the UVB-induced skin response.

Subject

Càncer de pell, ADN, Polimorfisme genètic, Radiació ultraviolada, Pell

Subject (English)

Skin cancer, DNA, Genetic polymorphisms, Ultraviolet radiation, Skin

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Centres Científics i Tecnològics de la Universitat de Barcelona (CCiTUB))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

MANILS PACHECO, Joan, et al. Multifaceted role of TREX2 in the skin defense against UV-induced skin carcinogenesis. Oncotarget. 2015. Vol. 6, num. 26, pags. 22375-22396. ISSN 1949-2553. [consulted: 14 of August of 2026]. Available at: https://hdl.handle.net/2445/113801

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